TY  - JOUR
AU  - Isermann, Tamara
AU  - Sers, Christine
AU  - Der, Channing J
AU  - Papke, Bjoern
TI  - KRAS inhibitors: resistance drivers and combinatorial strategies.
JO  - Trends in cancer
VL  - 11
IS  - 2
SN  - 2405-8033
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2025-00017
SP  - 91-116
PY  - 2025
N1  - 2025 Feb;11(2):91-116
AB  - In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRASG12C inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively. However, rather than marking the end of a successful assault on the Mount Everest of cancer research, this landmark only revealed new challenges in RAS drug discovery. In this review, we highlight the progress on defining resistance mechanisms and developing combination treatment strategies to improve patient responses to KRAS therapies.
KW  - KRAS (Other)
KW  - colorectal carcinoma (Other)
KW  - drug resistance (Other)
KW  - non-small cell lung cancer (Other)
KW  - pancreatic ductal adenocarcinoma (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39732595
DO  - DOI:10.1016/j.trecan.2024.11.009
UR  - https://inrepo02.dkfz.de/record/296069
ER  -